Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment
Cancer is the uncontrolled growth of abnormal cells in the body which form a mass known as a tumour. They have the capacity to develop their own blood vessels (angiogenesis) which supply the tumour with sufficient energy to grow (proliferation).
One in two people will be diagnosed with cancer in their lifetime, the benefits of exercise to prevent and treat cancer are well documented, with some listed below (Taken from American College of Sports Medicine Roundtable on Exercise Guidelines for Cancer Survivors). However, knowing what occurs at a molecular level is less extensively understood.
- Aerobic fitness
- Body composition
- Energy levels
- Quality of life
- Mental health
Tumour Growth Kinetics and Tumour Formation
There is great potential to control tumour growth through exercise with research suggesting this may be as high as a 67% reduction in growth rate. Using exercised conditioned serum to incubate cancers cells has shown to inhibit proliferation by 10-15%. This is because the molecular response to exercise effects the clonogenic potential of cancer cells by interfering with signalling events via the Hippo signalling pathway (affecting the process of angiogenesis). A takeaway message from this is that exercise at intensities associated with increases in catecholamines reduce the ability of cancer cells to proliferate and to form tumours in distant tissues having a potent effect on their metastatic potential.
In clinical reports the KI-67 proliferation index is used as a prognosis marker and predictor or reoccurrence as KI-67 is a protein in cells that increases as they prepare to divide into new cells. Literature on this topic has suggested three mechanisms, amongst others, by which exercise works to control tumour growth and thus the KI-67 proliferation index.
1. Tumour Metabolism
Tumours have an altered cell metabolism favouring aerobic glycolysis to support their high energy turnover. Exercising creates a redirection of energy substrates from the tumour to the metabolically active tissue so that muscular contractions can be sustained over time. Therefore, during periods of exercise the tumour becomes starved of energy and nutrients which impairs its ability to grow and spread.
2. Immunological Profile of the Tumour
Tumours have an immunological profile which prevents their natural degradation, they have the ability to paralyze the body’s infiltrating immune cells. Through exercise there is an increase capacity to mobilise and redistribute natural killer cells and cytotoxic T cells, two immune cells that play a role in the detection and removal of cancer cells.
As tumours favour aerobic glycolysis it means there is an accumulation of lactate within the cells which also inhibits immune cell function. Lactate is a bi product of aerobic glycolysis and through exercise there is an increased ability to lower intra-tumoral levels through the regulation of lactate dehydrogenase.
3. Exercise-Dependent Tumour-Organ Crosstalk
The function and trafficking of the immune cells mentioned above increase as body temperature increases. Therefore, through exercise and its associated increase in body temperature, blood vessels dilate and the vasculature becomes more permeable allowing for greater infiltration of natural killer cells and cytotoxic T cells.
To summarise these points, exercise has the capacity to reduce tumour growth through:
- Redistributing energy away from the tumour
- Increase the amount of immune cells
- Increase the number of immune cells that can infiltrate the tumour through an increase in body temperature and reducing the amount of lactate.